1st International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 26–28 June 1999 - San Diego, CA, USA

ART-ASSOCIATED INSULIN RESISTANCE: FREQUENCY, POTENTIAL CAUSES AND POSSIBLE THERAPEUTIC INTERVENTIONS

Antiviral Therapy 1999; 4(Suppl. 2):13 (abstract no. 5)

FD Goebel and R Walli
Ludwig-Maximilians-University, Munich,Germany

BACKGROUND: Insulin resistance (IR) is frequently seen under ART. However, the underlying mechanisms (e.g. primary defect or secondary event), potential long-term effects (e.g. cardiovascular risk) and possible therapeutic strategies are still unclear.

OBJECTIVES/METHODS: (i) Determination of the frequency and the time course of IR in HIV-infected patients prior to and during ART using an intravenous insulin tolerance test (ITT). (ii) Evaluation of the effect of treatment with troglitazone and of discontinuation of PI in patients with ART-associated IR. (iii) Evaluation of the expression of insulin receptors in muscle biopsies of patients under ART using immunohistochemistry and western blot analyses.

RESULTS: (i) IR was seen in 55% of patients under RTI+PI and in 27% of patients under RTI alone. In 13 of the PI-treated patients, worsening of IR was seen after 7-13 months (median 9), in two patients IR improved. (ii) In six patients with ART-associated diabetes and IR, troglitazone 400 mg once daily resulted in an amelioration (n=2) or even reversal (n=2) of IR, and had beneficial effects on fat maldistribution and dyslipidaemia (n=5). Alternatively, switching from a PI to an NNRTI or abacavir while continuing on RTI lead to an improvement of IR in the majority of patients. (iii) A decreased expression of insulin receptors could be demonstrated in muscle biopsies of patients with ART-associated IR, as compared to those with normal IS or controls (seronegative type-II diabetics with IR).

CONCLUSIONS: (i) IR is frequently seen under ART, not restricted to the use of PI and commonly worsens over time. (ii) Treatment with insulin sensitizers (e.g. thiazolidinediones), and in some cases discontinuing PI, can ameliorate ART-associated IR. (iii) Besides other mechanisms, decreased expression of insulin receptors might contribute to ART-associated IR.

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